Active cytomegalovirus (CMV) infection is usually seen in the immunosuppressed patient. Recent evidence suggests that this virus may cause life threatening pulmonary infection in the compromised host. In clinically apparent pulmonary infections, CMV is commonly found with other opportunistic pathogens. The frequency of this association and the mortality associated with pulmonary infections in the immunosuppressed host prompted this proposal to define the role of CMV as a pulmonary pathogen and to determine whether active infection with this virus increases the risk of pulmonary infection with other opportunistic pathogens. A guinea pig model will be used to examine a variety of parameters to determine the effect of this virus on host defense mechanisms. An examination of the effect of immunosuppressive agents on the natural history of infection will be examined in an attempt to simulate active CMV infection in the compromised human host. An analysis of the effect of CMV on pulmonary defense mechanisms will be studied. An in vitro analysis of the in vivo effects of CMV infection on macrophage and lymphocyte function will include an examination of macrophage chemotaxis, phagocytosis and intracellular killing; and lymphocyte transformation and cytotoxic capacity will be examined. The in vitro exposure of macrophages and lymphocytes to CMV and its effects on function will also be investigated. Finally, a study of the effect of CMV infection on pulmonary killing of inhaled pathogens will be undertaken.